The idea that increased levels of exhaled NO are related to a specific type of airway inflammation would be in keeping with lack of increase in other airway inflammatory disorders, such as ARDS, cystic fibrosis, and COPD, in which there is excess neutrophilic inflammation. This is somewhat surprising, as neutrophils are thought to produce far greater amounts of NO than the epithelium, endothelium, or eosinophils. The lack of increase in these conditions may be attributed to the substantial release of other reactive species, such as superoxide anion, which then chemically remove NO from detection in the exhaled gas. Asthma may therefore be the unique inflammatory airway condition that demonstrates increased exhaled NO levels by virtue of its underlying atopic nature. This could also explain why some untreated asthmatics do not have increased NO levels, because not all asthma has an atopic basis.
In conclusion, our study showed that within an Clinical Investigations asthmatic population, exhaled NO levels correlated with atopy in both steroid-treated and steroid-naive subgroups. This suggests that in asthmatics, increased NO production may be predominantly a feature of atopy.
Background: COPD is a complex disease with exacerbations characterized by worsening of symptoms resulting in deteriorating lung function.
Study objective: To assess predictive factors of relapse for patients with acute exacerbations of COPD (AECB).
Design: Retrospective cohort analysis of visits for AECB.
Setting: Veterans Affairs Medical Center.
Patients: Three hundred sixty-two visits (173 patients) with documented COPD treated as outpatients for AECB.
Measurements: Severity of underlying COPD, severity of AECB, comorbid conditions, therapy, and relapse rates (return visit within 14 days with persistent or worsening symptoms).
Results: Each visit was analyzed individually (referred to as a patient-visit). One group received antibiotics (270 patient-visits), and the second group (92 patient-visits) did not. Both groups had similar demographics and severity of underlying COPD. The overall relapse rate was 22%.
More on www.acanadianhealthcaremall.com
During the preparation of this article, a similar study was published by Simpson showing almost identical results. Our study extends their findings by demonstrating that the relationship between exhaled NO and atopy holds even for asthmatics receiving inhaled steroids. Because iNOS is steroid sensitive, the explanation for this observation is unclear. Could steroid-induced modification in exhaled NO correspond to steroid-induced reduction in atopic activity?
This is unlikely because although exhaled NO would be lowered by inhaled steroid use, it would not affect mast cell activity at sites other than the area of application and therefore should not influence skin-prick positivity and total IgE count. Further, we found no correlation between steroid dose and severity of atopy. Thus, it would seem that the relationship between exhaled NO and atopy shows a positive correlation, which is not the case with inhaled steroids and exhaled NO. This may be because the effect of atopy is much stronger than that of inhaled steroids and therefore overrides that of inhaled steroids. The suggestion could be that allergy-mediated production of NO, eg, from eosinophils or T helper-2 activation may be greater than that from neutrophils and inflamed epithelial cells and not as responsive to steroid treatment. However, it could also be hypothesized that iNOS expression in atopic asthmatics is less responsive to inhaled steroids, and therefore they continue to produce high levels of NO in the airways.
Putting our findings and those from the other studies in context of data on sputum and peripheral eosinophilia, it can be suggested that increased exhaled NO levels reflect a specific type of inflammation, that of T helper-2-driven inflammatory response rather than nonspecific airway inflammation. Increasing evidence suggests that airway inflammation in atopic asthma is associated with a T helper-2 cytokine profile, characterized by interleukin-4 and interleukin-5 production. These cytokines promote switching of B-cell isotypes to IgE production and activation of eosinophils, respectively. Interleukin-4 also appears to prolong the expression of iNOS in airway epithelium, providing a possible explanation for increased production of NO from the airways.